rs13436547

Variant names:

• chr5-172413721-G-A
• rs13436547
• NM_001017995.3:c.157-7369C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017995.3(SH3PXD2B):​c.157-7369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 152,286 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.061 (431 hom., cov: 33)
• Consequence: SH3PXD2B NM_001017995.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659
• Publications: 1 publications found

Genes affected

SH3PXD2B (HGNC:29242): (SH3 and PX domains 2B) This gene encodes an adapter protein that is characterized by a PX domain and four Src homology 3 domains. The encoded protein is required for podosome formation and is involved in cell adhesion and migration of numerous cell types. Mutations in this gene are the cause of Frank-ter Haar syndrome (FTHS), and also Borrone Dermato-Cardio-Skeletal (BDCS) syndrome. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

SH3PXD2B Gene-Disease associations (from GenCC):

• Frank-Ter Haar syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017995.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3PXD2B	NM_001017995.3	MANE Select	c.157-7369C>T		intron	N/A	NP_001017995.1
	SH3PXD2B	NM_001308175.2		c.157-7369C>T		intron	N/A	NP_001295104.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3PXD2B	ENST00000311601.6	TSL:1 MANE Select	c.157-7369C>T		intron	N/A	ENSP00000309714.5
	SH3PXD2B	ENST00000519643.5	TSL:1	c.157-7369C>T		intron	N/A	ENSP00000430890.1
	SH3PXD2B	ENST00000636523.1	TSL:5	c.112-7369C>T		intron	N/A	ENSP00000490082.1

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9328 AN: 152168 Hom.: 429 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00952

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0593

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0614 AC: 9344 AN: 152286 Hom.: 431 Cov.: 33 AF XY: 0.0580 AC XY: 4317 AN XY: 74462

African (AFR) AF: 0.135 AC: 5599 AN: 41540

American (AMR) AF: 0.0393 AC: 602 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 233 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00932 AC: 45 AN: 4828

European-Finnish (FIN) AF: 0.0279 AC: 296 AN: 10612

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0358 AC: 2434 AN: 68030

Other (OTH) AF: 0.0587 AC: 124 AN: 2114

Alfa AF: 0.0543 Hom.: 59

Bravo AF: 0.0655

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.8
DANN	Benign	0.88
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13436547; hg19: chr5-171840725;